Splenic but not thymic autoreactive T cells from New Zealand Black mice respond to a dominant erythrocyte Band 3 peptide

Abstract

Previous work from our laboratory suggested that erythrocyte Band 3 peptide 861-874 is the dominant epitope recognized by splenic T cells from adult New Zealand Black (NZB) mice that are developing autoimmune haemolytic anaemia (AIHA). Here, it is shown that splenic T cells from 6-week-old NZB mice mount a vigorous in vitro proliferative response to peptide 861-874 and some other selected Band 3 peptides. As the donors grow older, splenic T cells respond to an increasing number of Band 3 peptides and the magnitude of their response also becomes greater. Splenic T cells from 3-week-old NZB mice still responded vigorously to peptide 861-874 and Band 3. By contrast, neither thymocytes nor single-positive CD4-enriched thymus cells from NZB mice responded to peptide 861-874 or Band 3, although they responded to concanavalin A (Con A). However, thymocytes from mice expressing a transgenic T-cell receptor (TCR)-specific for myelin basic protein (MBP) peptide Ac 1-9 responded vigorously to Ac 1-9. It is considered that the T-cell response of NZB mice to Band 3 is initially focused on peptide 861-874 and later spreads to other Band 3 peptides as the disease progresses and that peptide 861-874-reactive T cells are primed in the periphery rather than the thymus.